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Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas

PURPOSE: The preoperative distinction between uterine leiomyoma (LM) and leiomyosarcoma (LMS) is difficult, which may result in dissemination of an unexpected malignancy during surgery for a presumed benign lesion. An assay based on circulating tumor DNA (ctDNA) could help in the preoperative distin...

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Autores principales: Przybyl, Joanna, Spans, Lien, Lum, Deirdre A., Zhu, Shirley, Vennam, Sujay, Forgó, Erna, Varma, Sushama, Ganjoo, Kristen, Hastie, Trevor, Bowen, Raffick, Debiec-Rychter, Maria, van de Rijn, Matt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Clinical Oncology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105159/
https://www.ncbi.nlm.nih.gov/pubmed/32232185
http://dx.doi.org/10.1200/PO.18.00409
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author Przybyl, Joanna
Spans, Lien
Lum, Deirdre A.
Zhu, Shirley
Vennam, Sujay
Forgó, Erna
Varma, Sushama
Ganjoo, Kristen
Hastie, Trevor
Bowen, Raffick
Debiec-Rychter, Maria
van de Rijn, Matt
author_facet Przybyl, Joanna
Spans, Lien
Lum, Deirdre A.
Zhu, Shirley
Vennam, Sujay
Forgó, Erna
Varma, Sushama
Ganjoo, Kristen
Hastie, Trevor
Bowen, Raffick
Debiec-Rychter, Maria
van de Rijn, Matt
author_sort Przybyl, Joanna
collection PubMed
description PURPOSE: The preoperative distinction between uterine leiomyoma (LM) and leiomyosarcoma (LMS) is difficult, which may result in dissemination of an unexpected malignancy during surgery for a presumed benign lesion. An assay based on circulating tumor DNA (ctDNA) could help in the preoperative distinction between LM and LMS. This study addresses the feasibility of applying the two most frequently used approaches for detection of ctDNA: profiling of copy number alterations (CNAs) and point mutations in the plasma of patients with LM. PATIENTS AND METHODS: By shallow whole-genome sequencing, we prospectively examined whether LM-derived ctDNA could be detected in plasma specimens of 12 patients. Plasma levels of lactate dehydrogenase, a marker suggested for the distinction between LM and LMS by prior studies, were also determined. We also profiled 36 LM tumor specimens by exome sequencing to develop a panel for targeted detection of point mutations in ctDNA of patients with LM. RESULTS: We identified tumor-derived CNAs in the plasma DNA of 50% (six of 12) of patients with LM. The lactate dehydrogenase levels did not allow for an accurate distinction between patients with LM and patients with LMS. We identified only two recurrently mutated genes in LM tumors (MED12 and ACLY). CONCLUSION: Our results show that LMs do shed DNA into the circulation, which provides an opportunity for the development of ctDNA-based testing to distinguish LM from LMS. Although we could not design an LM-specific panel for ctDNA profiling, we propose that the detection of CNAs or point mutations in selected tumor suppressor genes in ctDNA may favor a diagnosis of LMS, since these genes are not affected in LM.
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spelling pubmed-71051592020-03-30 Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas Przybyl, Joanna Spans, Lien Lum, Deirdre A. Zhu, Shirley Vennam, Sujay Forgó, Erna Varma, Sushama Ganjoo, Kristen Hastie, Trevor Bowen, Raffick Debiec-Rychter, Maria van de Rijn, Matt JCO Precis Oncol Original Reports PURPOSE: The preoperative distinction between uterine leiomyoma (LM) and leiomyosarcoma (LMS) is difficult, which may result in dissemination of an unexpected malignancy during surgery for a presumed benign lesion. An assay based on circulating tumor DNA (ctDNA) could help in the preoperative distinction between LM and LMS. This study addresses the feasibility of applying the two most frequently used approaches for detection of ctDNA: profiling of copy number alterations (CNAs) and point mutations in the plasma of patients with LM. PATIENTS AND METHODS: By shallow whole-genome sequencing, we prospectively examined whether LM-derived ctDNA could be detected in plasma specimens of 12 patients. Plasma levels of lactate dehydrogenase, a marker suggested for the distinction between LM and LMS by prior studies, were also determined. We also profiled 36 LM tumor specimens by exome sequencing to develop a panel for targeted detection of point mutations in ctDNA of patients with LM. RESULTS: We identified tumor-derived CNAs in the plasma DNA of 50% (six of 12) of patients with LM. The lactate dehydrogenase levels did not allow for an accurate distinction between patients with LM and patients with LMS. We identified only two recurrently mutated genes in LM tumors (MED12 and ACLY). CONCLUSION: Our results show that LMs do shed DNA into the circulation, which provides an opportunity for the development of ctDNA-based testing to distinguish LM from LMS. Although we could not design an LM-specific panel for ctDNA profiling, we propose that the detection of CNAs or point mutations in selected tumor suppressor genes in ctDNA may favor a diagnosis of LMS, since these genes are not affected in LM. American Society of Clinical Oncology 2019-10-16 /pmc/articles/PMC7105159/ /pubmed/32232185 http://dx.doi.org/10.1200/PO.18.00409 Text en © 2019 by American Society of Clinical Oncology https://creativecommons.org/licenses/by/4.0/ Licensed under the Creative Commons Attribution 4.0 License: https://creativecommons.org/licenses/by/4.0/
spellingShingle Original Reports
Przybyl, Joanna
Spans, Lien
Lum, Deirdre A.
Zhu, Shirley
Vennam, Sujay
Forgó, Erna
Varma, Sushama
Ganjoo, Kristen
Hastie, Trevor
Bowen, Raffick
Debiec-Rychter, Maria
van de Rijn, Matt
Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas
title Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas
title_full Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas
title_fullStr Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas
title_full_unstemmed Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas
title_short Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas
title_sort detection of circulating tumor dna in patients with uterine leiomyomas
topic Original Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105159/
https://www.ncbi.nlm.nih.gov/pubmed/32232185
http://dx.doi.org/10.1200/PO.18.00409
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